Li Xu, Li Xiwen, Ren Yanlin, Wang Ling, Mao Zehao, Gao Shikun, Ma Peng, Chen Junjie
Department of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China.
Clinical Medical Research Center, Affiliated Hospital of Nantong University, Nantong, China.
Front Mol Biosci. 2025 Apr 11;12:1566293. doi: 10.3389/fmolb.2025.1566293. eCollection 2025.
The histone chaperone Holliday Junction Recognition Protein (HJURP) has been associated with multiple types of cancers, but its role in GC is not yet fully understood. Considering its functions in centromere stability and DNA repair, investigating HJURP's role in GC may offer novel therapeutic perspectives.
HJURP expression was examined in a dataset comprising TCGA-STAD samples and an internal group of GC patients, utilizing RNA sequencing and Western blot techniques. Functional experiments were carried out on the AGS and HGC-27 GC cell lines. The expression levels of HJURP, MYC, and Topoisomerase II alpha (TOP2A) were assessed via quantitative real-time PCR and Western blot. Proliferation rates of the cells were determined through EdU, CCK-8, and colony formation assays.
Compared to adjacent normal tissues, HJURP expression was notably increased in GC tissues, a finding consistent across both the TCGA-STAD database and our internal patient group. Silencing HJURP markedly reduced GC cell growth and chemoresistance. Mechanistically, HJURP enhanced MYC stability, which in turn promoted TOP2A transcription. Rescue experiments confirmed that overexpression of TOP2A alters proliferation and chemoresistance of GC cells with HJURP knockdown, indicating the dependency of this axis on MYC activity.
Our study demonstrates that HJURP is critical for promoting GC proliferation and chemoresistance through the regulation of the MYC/TOP2A transcriptional network. Targeting HJURP might offer a novel therapeutic avenue for GC, necessitating further exploration of its clinical potential. This work underscores the value of investigating histone chaperones as potential targets in cancer treatment.
组蛋白伴侣霍利迪连接点识别蛋白（HJURP）已与多种类型的癌症相关联，但其在胃癌（GC）中的作用尚未完全明确。鉴于其在着丝粒稳定性和DNA修复中的功能，研究HJURP在GC中的作用可能会提供新的治疗前景。
利用RNA测序和蛋白质印迹技术，在一个包含TCGA-STAD样本和一组内部GC患者的数据集里检测HJURP的表达。在AGS和HGC-27 GC细胞系上进行功能实验。通过定量实时PCR和蛋白质印迹评估HJURP、MYC和拓扑异构酶IIα（TOP2A）的表达水平。通过EdU、CCK-8和集落形成实验测定细胞的增殖率。
与相邻正常组织相比，HJURP在GC组织中的表达显著增加，这一发现与TCGA-STAD数据库和我们的内部患者组一致。沉默HJURP显著降低了GC细胞的生长和化疗耐药性。从机制上讲，HJURP增强了MYC的稳定性，进而促进了TOP2A的转录。挽救实验证实，TOP2A的过表达改变了HJURP敲低的GC细胞的增殖和化疗耐药性，表明该轴对MYC活性的依赖性。
我们的研究表明，HJURP通过调节MYC/TOP2A转录网络对促进GC增殖和化疗耐药性至关重要。靶向HJURP可能为GC提供一种新的治疗途径，需要进一步探索其临床潜力。这项工作强调了研究组蛋白伴侣作为癌症治疗潜在靶点的价值。
